祁天花粉化学成分及药理作用研究

祁天花粉是临床常用中药之一,含有皂苷、天花粉蛋白、瓜氨酸等化学成分,在抗肿瘤、治疗糖尿病、降血糖等方面发挥了较为重要的作用,本文对其化学成分和药理作用简单综述,为祁天花粉的后续研究工作奠定基础和提供参考。     

中药白花蛇舌草有效成分的抗肿瘤作用机制研究

近年来国内外研究表明,白花蛇舌草中萜类、蒽醌类、黄酮类、多糖类、甾醇类等活性成分具有明显的抗肿瘤作用,其作用途径较为广泛,可通过抑制肿瘤细胞生长、诱导肿瘤细胞凋亡、调控细胞能量、增强机体免疫功能等发挥抗肿瘤作用。对中药白花蛇舌草有效成分的抗肿瘤作用机制研究进行综述,旨在为今后研究提供参考。     

中药诱导肿瘤细胞凋亡机制研究进展

中药及其生物活性成分具有毒副作用小、无残留、药理作用独特等特点,在抗肿瘤研究方面,已经成为抗肿瘤药物或其辅助药物,目前研究的热点是中药治疗肿瘤作用机制的研究。论文从单味中药及其有效成分、中药复方诱导肿瘤细胞凋亡机制等方面对中药诱导细胞凋亡在肿瘤的发生、发展和转归中所起的作用进行了综述。中药可以诱导肿瘤细胞凋亡,其可能的作用机制是通过调控原癌基因和抑癌基因的表达、影响细胞凋亡通路的信号传导及阻滞肿瘤细胞增殖周期等抑制肿瘤细胞的永生化。     

中药药物血清抗肿瘤研究进展

分别从促进肿瘤细胞凋亡,和对肿瘤细胞分化、肿瘤细胞内钙离子浓度、肿瘤细胞耐药性的影响,以及抑制肿瘤细胞端粒酶活性、抑制肿瘤细胞增殖、协同细胞毒化疗等方面进行了分析,并对目前中药药物血清抗肿瘤研究中存在的问题进行了阐述.     

家蚕BmNPV多角体蛋白与大肠杆菌L-天冬酰胺酶Ⅱ的融合表达

L-天冬酰胺酶是一种重要的蛋白类抗肿瘤药物,可通过降解L-天冬酰胺从而抑制肿瘤细胞中蛋白质的正常合成,导致肿瘤细胞的死亡.通过基因融合的方法,将大肠杆菌的asp基因在家蚕杆状病毒中表达,其活性进一步提高到5 940U/mg,为利用家蚕生物反应器生产该蛋白打下了基础.     

苦马豆素抗肿瘤作用研究进展

苦马豆素(SW)是一种吲哚里西啶生物碱,最早是从灰苦马豆中分离得到,是疯草类植物的主要毒性成分.它能抑制肿瘤细胞表面糖蛋白的表达,从而抑制肿瘤细胞的生长与转移.此外,SW能促进脾细胞增殖,增强巨噬细胞对肿瘤细胞的杀伤活性,还能促进机体淋巴细胞活性升高,刺激机体骨髓细胞增殖,增强机体杀灭肿瘤细胞的能力.由于SW具有很好的抗肿瘤活性和免疫增强作用,已引起国内外学者的广泛关注,并作为抗肿瘤药物筛选的后备药物.目前,国外SW抗肿瘤药物的研发已进入Ⅲ期临床试验阶段,而国内才刚起步.论文主要介绍了SW抗肿瘤作用及其临床治疗效果,并对SW下一步研究重点及应用前景进行了展望.     

抗肿瘤中药及其有效成分的作用研究现状

中药是祖国医学理论中重要的组成部分,几千年来为保障我国人民和动物的机体健康做出了巨大的贡献。近年来,肿瘤的发病率不断增高,逐渐成为人类和动物健康的大敌。由于中药与化学合成药物相比有着取材方便、价格低廉和毒副作用小等优点,中药及其有效成分抗肿瘤的机理研究已成为当今医学研究的热点。中药及其有效成分防治肿瘤是通过多靶点、多途径、多环节来实现的,其抗肿瘤的作用机理主要包括调节机体免疫功能、抑制肿瘤血管生长、诱导肿瘤细胞凋亡、诱导肿瘤细胞分化、逆转肿瘤细胞多重耐药性、调节肿瘤细胞信号传导、抑制端粒酶活性和细胞毒作用等。中药及其有效成分必将为人类和动物肿瘤的治疗开辟新的途径。     

甘肃棘豆生物碱抑制小鼠肝癌H22的生长及机理试验

甘肃棘豆(Oxytropis Kansuensis Bunge)是豆科棘豆属植物,其研究已历经百年,在积极探讨其防除和综合利用的同时,大量研究结果表明,其生物碱部位具有明显的抗肿瘤活性[1-3].本试验以荷H22肝癌肿瘤小鼠为模型,进一步研究证实其抗肿瘤活性;并在细胞学水平观察甘肃棘豆生物碱阻止H22细胞恶性表型及直接杀伤肿瘤细胞的作用,在分子生物学水平观察与恶性肿瘤发生发展过程密切相关的增殖细胞核抗原(PCNA)、突变型p53蛋白表达及生物碱的干预作用,为研究甘肃棘豆生物碱抑制肿瘤活性机理提供科学依据.     

新牛蛙抗肿瘤肽RGD-T-La(FS)嵌合体的设计及其抗肿瘤作用

为了研究新牛蛙抗肿瘤肽RGD-嵌合体的抗肿瘤作用及其对肿瘤细胞的作用机制。本研究以新牛蛙抗菌肽Temporin-La(T-La)为基序,通过生物信息学分析,改变特定氨基酸残基设计合成新的抗肿瘤肽Temporin-La(S)(TLa(S))和Temporin-La(FS)(T-La(FS)),氨基端偶联RGD肽成RGD-T-La、RGD-T-La(S)和RGD-T-La(FS)抗肿瘤肽,通过圆二色谱检测多肽二级结构,MTT法体外筛选抗肿瘤细胞活性多肽。使用流式细胞仪测定不同肿瘤细胞对不同多肽的吸收量,筛选对抗肿瘤肽敏感的肿瘤细胞。利用激光共聚焦显微镜实时观察抗肿瘤活性强的抗肿瘤肽对敏感肿瘤细胞的杀伤作用,并用扫描电镜观察抗肿瘤肽及其RGD嵌合体肽对肿瘤细胞的作用机制。在新牛蛙抗菌肽Temporin-La基序上设计T-La(S)和T-La(FS)2种抗肿瘤活性肽,圆二色谱仪测定其二级结构均呈α螺旋型,MTT结果显示黑色素瘤细胞(B16)对几种多肽的敏感性最强,10 mg/L质量浓度时,RGD-T-La(FS)对B16的毒性作用最强,细胞存活率为24.65%。激光共聚焦显微镜实时观察到,RGD-La(FS)和RGD-La(S)对肿瘤细胞都有较强的杀伤作用。扫描电镜结果显示,RGD嵌合体多肽对肿瘤细胞的杀伤作用具有位点靶向性。流式细胞仪检测HepG2对FITC-RGD-T-La(FS)的吸收量最大,检测到荧光强度为800 950.70。经改造的多肽T-La(FS)可以增加其对肿瘤细胞的杀伤作用,且偶联RGD的嵌合体RGD-T-La(FS)对肿瘤细胞的杀伤作用更具有靶向专一性,为抗肿瘤肽作为抗肿瘤药物的临床应用提供科学依据。     

异荭草素抗肿瘤药理作用及其机制的研究

异荭草素是从植物中提取的含有黄酮类活性成分的化合物。研究表明,异荭草素具有多种药理作用,不仅可以抗氧化、抗炎、抗病毒,还具有良好的抗肿瘤活性。异荭草素可通过干扰肿瘤细胞增殖、诱导肿瘤细胞凋亡、调控活性氧水平、诱导肿瘤细胞自噬、阻碍肿瘤细胞浸润和转移等途径发挥抗肿瘤作用。现将异荭草素的抗肿瘤作用及其机制的相关研究进展进行综述。     

天花粉蛋白对黄牛产后胎衣脱落及受胎率的影响

以淮北黄牛为对象，在正常分娩后不同时间，用生理盐水溶解天花粉蛋白胶囊，而后灌注入黄牛子宫粘膜与胎衣之间，观察其对胎衣脱落及受胎率的影响。结果，分娩后４，１２ｈ给药组及对照组，用药后胎衣脱落时间分别为４．５９，９．１５ｈ及５６．０８ｈ；胎衣完整率为９０．７％，８７．８％及６８．６％；产后首次发情时间平均为６０．７５，６６．２９ｄ及７４．７５ｄ；试验组与对照组差异极显著（Ｐ＜０．０１）。两试验组与对照组比较，１次受胎率分别提高３３．９８％和２７．６７％；２次受胎率提高３７．９４％和２８．５８％；３次受胎率提高２３３．２９％和１９９．９４％。结果显示，天花粉蛋白能促进胎衣及时完整地排出，并显著提高受胎率     

新牛蛙活性肽Catesbeianin-1a的抗菌抗肿瘤作用

通过筛选牛蛙皮肤cDNA文库得到具有较强抗菌抗肿瘤活性肽Catesbeianin-1a,合成其成熟肽氨基酸序列,MIC法测定抑菌活性结果表明,Catesbeianin-1a对临床常见的致病菌具有较强的抑菌活性,其中对猪链球菌2型的MIC为2.5mg/L,且对兔红细胞几乎无溶血性。MTT法测定多肽抗肿瘤细胞活性,结果 Catesbeianin-1a对胃癌细胞和肝癌细胞的抑杀活性很强,对肝癌细胞SGC7901的IC50为0.845mg/L。制作透射电镜超薄切片,利用透射电镜观察活性肽对细菌和肿瘤细胞超微结构的影响,旨在初步探讨牛蛙皮肤活性肽Catesbeianin-1a抗菌、抗肿瘤的作用机制,并以Catesbeianin-1a为基础进行分子改造来提高其抗肿瘤的靶向性并降低其毒性。     

华蟾毒精对胃腺癌细胞MGC-803作用的研究

研究华蟾毒精（cinobufagin,CBG）体外对人胃腺癌细胞MGC-803的抑制作用,并初步探讨其抗肿瘤的作用机制。MTT法测定CBG对胃腺癌MGC-803细胞的生长抑制情况;采用光镜观察CBG对人胃腺癌细胞MGC-803形态的影响;流式细胞术检测CBG对MGC-803细胞的抑制作用、细胞周期及细胞早期凋亡的影响。一定浓度范围内CBG对MGC-803细胞的增殖有剂量、时间依赖性抑制作用;光镜下可见细胞形态明显发生变化,细胞变圆,分泌颗粒增多,细胞折光性下降,大部分细胞脱壁;流式细胞仪检测MGC-803细胞,G1期细胞减少,大量细胞停滞在G2/M期,凋亡细胞增多。CBG对MGC-803细胞的抑制作用与诱导其细胞阻滞及凋亡密切相关。     

Effect of natural and synthetic retinoids on the proliferation and differentiation of three canine melanoma cell lines

The effect of two natural retinoids and synthetic retinoids with or without retinoid synergists on the proliferation and differentiation of 3 melanoma cell lines were investigated in vitro. No retinoids showed significant growth inhibitory effect on these cell lines when used alone, however, cell differentiation and significant growth inhibition were observed when treated with a combination of retinoids and a retinoid synergist. This study may suggest that, though the cells showed low susceptibilities when retinoids were treated alone, the combination of retinoids and a retinoid synergist may be effective to control the growth of canine melanoma cell lines.     

Sorafenib inhibits tumor cell growth and angiogenesis in canine transitional cell carcinoma

Canine transitional cell carcinoma (cTCC) is the most common naturally occurring bladder cancer and accounts for 1–2% of canine tumors. The prognosis is poor due to the high rate of invasiveness and metastasis at diagnosis. Sorafenib is a multi-kinase inhibitor that targets rapidly accelerated fibrosarcoma (RAF), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor-β (PDGFR-β), and KIT. In previous studies, a somatic mutation of B-rapidly accelerated fibrosarcoma (BRAF) and expressions of VEGFR-2 and PDGFR-β were observed in over 80% of patients with cTCC. Therefore, in this study, we investigated the anti-tumor effects of sorafenib on cTCC. Five cTCC cell lines were used in the in vitro experiments. All five cTCC cell lines expressed VEGFR-2 and PDGFR-β and sorafenib showed growth inhibitory effect on cTCC cell lines. Cell cycle arrest at the G0/G1 phase and subsequent apoptosis were observed following sorafenib treatment. In the in vivo experiments, cTCC (Sora) cells were subcutaneously injected into nude mice. Mice were orally administered with sorafenib (30 mg/kg daily) for 14 days. Sorafenib inhibited tumor growth compared to vehicle control. The necrotic area in the tumor tissues was increased in the sorafenib-treated group. Sorafenib also inhibited angiogenesis in the tumor microenvironment. Thus, sorafenib may be potential therapeutic agent for cTCC via its direct anti-tumor effect and inhibition of angiogenesis.     

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.     

盐酸小檗碱与左氧氟沙星联合抑制MRSA及其机制研究

养殖场抗生素滥用造成多种耐药性细菌的产生,从奶肉类制品中分离出耐甲氧西林金黄色葡萄球菌（MRSA）的案例逐年增长,对养殖业食品安全造成巨大威胁。本研究筛选出与左氧氟沙星具有联合抑制MRSA效果的天然产物盐酸小檗碱（BBR）,探究BBR与其对MRSA的协同抑菌效果和联合抑菌机制。结果表明,BBR能有效抑制MRSA生长,提高MRSA对左氧氟沙星的敏感度,两者联用后,MRSA对左氧氟沙星的MIC降为之前的1/16。协同作用机制主要为上调ribA及下调mec A和msc L表达水平,破坏细胞壁、增加细胞膜的通透性,从而达到协同抑菌的目的。本研究有助于降低畜牧养殖中抗生素的使用,为提高肉奶类食品安全奠定基础。     

Anti-tumor effect of adenoviral vector-mediated p53 gene transfer on the growth of canine osteosarcoma xenografts in nude mice

We evaluated the anti-tumor effect of adenoviral vector-mediated p53 gene therapy on the growth of canine osteosarcoma xenografts formed in nude mice. Nude mice were subcutaneously transplanted with cells of 2 P53 mutant canine osteosarcoma cell lines, POS and CHOS. The osteosarcoma xenografts were injected with either an adenoviral vector that expresses canine wild-type P53 (AxCA-cp53) or LacZ (AxCA-LacZ). Tumor growth was significantly inhibited in the xenografts injected with AxCA-cp53 in comparison to those injected with AxCA-LacZ or PBS during the observation period of 27 days. An increase of the amount of p21(WAF1/CDKN1A) mRNA, and the number of apoptotic cells was shown in the tumors injected with AxCA-cp53 in comparison to those injected with AxCA-LacZ or PBS. The present study revealed that the adenoviral vector-mediated p53 gene transfer had an anti-tumor effect in canine osteosarcoma xenografts formed in nude mice.     

Obstacles to T cell migration in the tumor microenvironment

These last years, significant progress has been made in the design of strategies empowering T cells with efficient anti-tumor activities. Hence, adoptive T cell therapy and the use of monoclonal antibodies against the immunosuppressive surface molecules CTLA-4 and PD-1 appear as the most promising immunotherapies against cancer. One of the challenges ahead is to render these therapeutic interventions even more effective as a still elevated fraction of cancer patients is refractory to these treatments. A frequently overlooked determinant of the success of T cell-based immunotherapy relates to the ability of effector T cells to migrate into and within tumors, as well as to have access to tumor antigens. Here, we will focus on recent advances in understanding T cell trafficking into and within tumors. Both chemoattractant molecules and structural determinants are essential for regulating T cell motile behavior along with cellular interactions-mediated antigen recognition. In addition, we will review evidence that the microenvironment of advanced tumors creates multiple obstacles limiting T cells from migrating and making contact with their malignant targets. We will particularly focus on the extracellular matrix and tumor-associated macrophages that make tumors a hostile environment for T cell ability to contact and kill malignant cells. Finally, we will discuss possible strategies to restore a tumor microenvironment more favorable to T cell migration and functions with a special emphasis on approaches targeting the dysregulated extracellular matrix of growing tumors.